THE POLYADENYLATION FACTOR CSTF-64 REGULATES ALTERNATIVE PROCESSING OF IGM HEAVY-CHAIN PRE-MESSENGER-RNA DURING B-CELL DIFFERENTIATION

The switch from membrane-bound to secreted-form IgM that occurs during differentiation of B lymphocytes has long been known to involve regul ated processing of the heavy chain pre-mRNA. Here, we show that accumu lation of one subunit of an essential polyadenylation factor (CstF-64) is specifically repressed in mouse primary B cells and that overexpre ssion of CstF-64 is sufficient to switch heavy chain expression from m embrane-bound (mu m) to secreted form (mu s). We further show that Cst F-64 is limiting for formation of intact CstF, that CstF has a higher affinity for the pm poly(A) site than for the mu s site, and that the mu m site is stronger in a reconstituted in vitro processing reaction. Our results indicate that CstF-64 plays a key role in regulating IgM heavy chain expression during B cell differentiation.